Arthritis is the most common chronic diseases in the world. There are many causes of arthritis, and the joint damage caused by arthritis is also different. Currently, Tofacitinib (CP-690550) is a novel oral JAK (Janus Kinase) pathway inhibitor developed by Pfizer Inc., and Tofacitinib is a first-in-class drug developed for rheumatoid arthritis treatment. Since Tofacitinib was produced in Pfizer's laboratories, the drug was highly expected to be a blockbuster drug. The success of the drug will be a big victory for the widely criticized research and development business of Pfizer. The results of Phase III clinical trials showed that the efficacy of Pfizer's Tofacitinib was significantly better than that of methotrexate.

Based on the structure of Tofacitinib, a series of JAK inhibitor compounds, which are active in vitro and in vivo and are highly absorbable, have been developed. See WO2013091539. The compounds disclosed in WO2013091539 were screened and prepared as salts in which (3aR,5s,6aS)—N-(3-methoxyl-1,2,4-thiadiazole-5-yl)-5-(methyl(7H-pyrrolo[2,3-d]pyrimidine-4-yl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-formamide bisulfate of formula (I) was obtained, and its preparation method was disclosed in PCT Patent Application No. PCT/CN2014/076794 (an application previously filed by the applicant). The compound of formula (I) is expected to be a preferred compound of JAK inhibitors, and has important study significance for the treatment of rheumatic and rheumatoid arthritis.
The crystal structure of the pharmaceutically active ingredient often affects the chemical stability of the drug. Different crystallization conditions and storage conditions can lead to changes in the crystal structure of the compound, and sometimes the accompanying production of other forms of crystal form. In general, an amorphous drug product does not have a regular crystal structure, and often has other defects such as poor product stability, smaller particle size, difficult filtration, easy agglomeration, and poor liquidity. Thus, it is necessary to improve the various properties of the above product. There is a need to identify a new crystal form with high purity and good chemical stability.